EMMPRIN-mediated MMP regulation in tumor and endothelial cells
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Tumor invasion and metastasis are multistep processes which require extracellular matrix remodeling by proteolytic enzymes such as matrix metalloproteinases (MMPs). The production of these enzymes is stimulated by many soluble or cell-bound factors. Among these factors, extracellular matrix metalloproteinase inducer (EMMPRIN) is known to increase in vitro stromal cell production of MMP-1, MMP-2 and MMP-3. In this study, we demonstrated that EMMPRIN-transfected MDA-MB-436 tumor cells displayed a more invasive capacity than vector-transfected cells in a modified Boyden chamber invasion assay. Using gelatin zymography and protein analyses, we showed that EMMPRIN-transfected cancer cells produced significantly more latent and active MMP-2 and MMP-3 than vector-transfected cancer cells. We found that EMMPRIN did not regulate MMP-1, MMP-9, membrane type-1 MMP (MT1-MMP) expression and had also no effect on the production of the specific tissue inhibitors of MMPs (TIMPs), TIMP-1 and TIMP-2. We also demonstrated that tumor-derived EMMPRIN stimulated MMP-1, -2, and -3 without modification of MMP-9, MT1-MMP, TIMP-1 and TIMP-2 production in human umbilical vein endothelial cells (HUVEC). These data provide support for the role of EMMPRIN in tumor invasion, metastasis, and neoangiogenesis by stimulating extracellular matrix remodeling around tumor cell clusters, stroma, and blood vessels.
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- EMMPRIN-mediated MMP regulation in tumor and endothelial cells
Clinical & Experimental Metastasis
Volume 19, Issue 8 , pp 697-702
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- Print ISSN
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- Kluwer Academic Publishers
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- tumor invasion
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- Author Affiliations
- 1. Inserm U514, IFR53, CHU Maison-Blanche, Reims, France
- 2. Departments of Research and Medicine, Veterans Administration Medical Center, Northport, New York, USA
- 3. Department of Anatomy and Cellular Biology, Tufts University, Boston, Massachusetts, USA